tbuckley/cabot-search huggingface dataset:
Outcomes of transarterial chemoembolization in neoadjuvant therapy of patients with gastric cancer: A multicenter retrospective cohort study.
Authors: Jiang Min, Wei Zhang
Journal: Journal of Clinical Oncology (2023)

410 Background: Gastric cancer is one of the most common cancers globally. About half of new cases were reported in China, and the most cases are advanced gastric cancer. According to treatment guideline, gastric cancers with pT3-4, any N or any pT, N+ are recommended to fluoropyrimidine based preoperative/neoadjuvant chemotherapy, followed by D2 resection and adjuvant chemotherapy, however, the five-years survival rate remain only 30%~50%. Methods: We had a multi-center retrospective cohort study about outcome of 43 gastric cancers with pT3-4, any N treated by Transarterial Chemoembolizaion (TACE) in neoadjuvant chemotherapy between October 2018 and June 2019. The procedure of TACE is that nutrition artery of tumor, usually left, right or right gastroomental artery, was injected into Oxaliplatin (130mg/m2) in DSA, follow by 2ml Iodized Oil Granules. After TACE, patients had S1 from D1 to D14, cycled every 21 days. And then, patients had another above-mentioned TACE+oral S1 procedure, followed by a systemic chemotherapy regimen SOX (Oxaliplatin was injected through vein). After that, a D2 resection (If tumor can be resected) was given to the patients. 3 cycles adjuvant chemotherapy (SOX regimen) were given to patients after operation. Results: 42/43 (97.7%) patients have D2 resection successfully, and 1/42 patient went to systemic chemotherapy because liver metastasis was found before second TACE treatment. According to pathological analysis about the tumor tissues after resection, TRG (Tumor response grade) 0 was 25 in 42 (59.5%); TRG 1 was 10 (23.8%); TRG 2 was 5 (11.9%) and TRG 3 was 2 (4.8%). Anastomotic leak was reported in 3/42 (7.14%); abdominal infection anastomotic leak was in 4/42 (9.5%); no bleeding was reported. All patients were recovered after symptomatic treatment. No death was reported because of the short-term complications. 3-years PFS was 64.2% (95% CI: 60-69), 5 patients had local recurrence, 7 patients had distant recurrence and 3 patients had both. 3-years OS was 71.4% (95% CI: 65-75). Conclusions: TACE used in neoadjuvant therapy of patients with gastric cancer was safe, and shown as a promising method for improving the survival prognosis.
Democratizing access to research for patients with pancreatic cancer across a diverse health system through natural language processing of radiology reports.
Authors: Daniel King, Cristina Valente, Matthew Barish, Anthony Carvino
Journal: Journal of Clinical Oncology (2023)

664 Background: Access to clinical trials and translational research studies is integral to improving cancer care for pancreatic cancer. The in-patient setting is a valuable opportunity to obtain research specimens and establish transition to out-patient oncology. However, samples coordinators rarely have sufficient lead time prior to biopsy to consent patients and be present for tissue collection. Meanwhile, histopathology of biopsied specimens may not be complete prior to discharge, hindering follow-up planning. Polyethnic-1000 is a research study enrolling African American patients with pancreatic cancer, is a priority study for our institution, and was the target study that motivated the below innovative strategy to better obtain research samples and ensure adequate follow-up. Methods: We observed recurrent suspicious abnormalities on abdominal radiology reports that foreshadow subsequent biopsy of the pancreas. To explore this further, we trained a natural language classifier to identify radiology reports as suspicious for pancreatic cancer. The pretrained model used is RadBERT, a custom-built language model based on Google’s BERT and further pretrained on several million radiology text reports. A gastrointestinal oncologist, clinical research coordinator, and radiologist informatician curated a dataset consisting of 1136 CT abdominal radiology reports, among which 696 were considered suspicious for pancreatic cancer. Among this curated database of reports, a training set consisting of 908 reports was used to fine-tune the RadBERT base model and produce our pancreatic cancer suspicion classifier. A validation and test dataset each consisting of 114 cases were reserved for model evaluation. We computed the final classifier performance metrics over the test dataset. Results: The model obtained an accuracy of 92%, and produced an F1 score of 0.936, a recall of 0.943, and a precision of 0.930. Conclusions: An early iteration model to classify CT abdominal radiology reports was highly accurate and has the potential to substantially increase identification of patients who may be suitable for clinical research studies and trials. We are now working to improve and expand our dataset in order to train classifiers with greater and more robust performance, while simultaneously developing an automated near real-time process that will leverage our models to identify reports suspicious for pancreatic cancer and then notify a coordinator and navigator.
Prognostic value of mismatch repair deficiency in patients receiving first-line fluoropyrimidine plus platinum chemotherapy for metastatic, recurrent, or locally advanced unresectable gastric cancer.
Authors: Chung Ryul Oh, Eo Jin Kim, Heejung Chae, Young Soo Park, Min-Hee Ryu, Hyung-Don Kim, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2023)

461 Background: In localized gastric cancer (GC), deficient mismatch repair (dMMR) tumors reportedly have a favorable prognosis. However, a potentially detrimental effect of the dMMR status was suggested in patients treated with adjuvant chemotherapy. It remains unclear whether the mismatch repair (MMR) status can impact clinical outcomes in patients with metastatic GC (mGC) receiving palliative chemotherapy. We examined the impact of the MMR status on survival outcomes of patients with HER2-negative mGC receiving first-line fluoropyrimidine plus platinum (FP) chemotherapy. Methods: We reviewed patients with histologically confirmed metastatic, recurrent, or locally advanced unresectable adenocarcinoma of the stomach or gastroesophageal junction receiving first-line FP chemotherapy between January 2015 and August 2018 at Asan Medical Center, Korea. MMR status was correlated with clinical characteristics and survival outcomes for patients with available MMR immunohistochemistry results. Results: Of 895 patients, we analyzed 543 with available MMR protein expression results, and dMMR was detected in 4.4% (n=24). Patients with dMMR exhibited a significantly higher median age than those with proficient MMR (pMMR) (64 vs. 58 years, p=0.044). No signet ring cell carcinoma (SRCC) was detected among dMMR tumors, whereas SRCC was found in 17.5% of pMMR tumors. Based on our prognostic model (Koo DH et al, 2011), only 4.2% of patients with dMMR were classified as the poor-risk group (vs. 16.8% of patients with pMMR, p=0.097). No significant difference in progression-free survival (PFS) was noted between patients with dMMR and pMMR tumors (median, 5.6 vs. 5.8 months, p=0.266). Patients with dMMR tumors tended to have better overall survival than those with pMMR tumors; this difference was not statistically significant (median, 17.9 vs. 12.2 months, p=0.183). In the good-risk subgroup, patients with dMMR tumors had a significantly worse PFS than those with pMMR tumors (median, 5.6 vs. 9.2 months, p=0.009); multivariate analysis revealed that MMR status was an independent factor for poor PFS in this subgroup. Conclusions: Survival outcomes of dMMR mGC did not differ from pMMR in patients who received first-line FP chemotherapy. However, in the good-risk subgroup, patients with dMMR tumors had a significantly shorter PFS than those with pMMR, suggesting a potentially reduced efficacy of cytotoxic chemotherapy in these patients.
Effect of resection margin status on recurrence pattern and survival in distal pancreatectomy for left-sided pancreatic ductal adenocarcinoma.
Authors: Jaewoo Kwon, Sung Ryol Lee, Jun Ho Shin, Song Cheol Kim
Journal: Journal of Clinical Oncology (2023)

675 Background: The association of resection margin status with recurrence and survival after pancreatectomy for pancreas ductal adenocarcinoma (PDAC) remains controversial. The aim of this study was to identify the effect of R1 resection on recurrence pattern and survival after distal pancreatectomy for left-sided PDAC. Methods: Patients who underwent distal pancreatectomy for PDAC at two high-volume institutions between January 2010 and December 2017 were retrospectively reviewed. Perioperative characteristics, pathological outcomes, recurrence pattern and survival data were collected to compare R0 resection and R1 resection. Results: Among 558 patients who underwent distal pancreatectomy for PDAC, 158 patients (28.3%) showed R1 resection margin. R1 patients were associated with large tumor size (3.3 cm vs. 3.7 cm, p= 0.006) and lower number of positive lymph nodes (1.3 vs. 2.0, p= 0.001). Median overall survival (37.3 months vs. 20.1 months, p&lt; 0.001) and recurrence-free survival (14.6 months vs. 6.9 months, p&lt; 0.001) significantly differed between the R0 and R1 groups. Disease recurrence patterns were not statistically different between the two groups ( p = 0.182). Among the recurrence patterns, peritoneal carcinomatosis had the shortest recurrence-free survival (5.6 months, p &lt; 0.05) and overall survival (13.6 months, p &lt; 0.05) compared with all other recurrence patterns. Conclusions: R1 resection margin after distal pancreatectomy was associated with poor survival and early recurrence. There is no significant difference in recurrence pattern between R0 and R1. Among the recurrence patterns, peritoneal carcinomatosis showed the worst prognosis.
Identification of HER2+ malignant cells in gastric tumors from single-cell RNAseq data.
Authors: Zhiming Zhang, Xiufeng Yang
Journal: Journal of Clinical Oncology (2023)

417 Background: Gastric cancer is the 4th leading cause of cancer death worldwide with high incidence in East Asia. Despite recent developments in treatment options, gastric cancer survival rate remains low, partially attribute to tumor heterogeneity. Here we performed a comprehensive single cell analysis of malignant cells from gastric tumor samples. In addition to characterizing heterogenous transcriptional patterns, we developed a framework to identify HER2+ malignant cells, which may complement standard diagnostics for treatment decisions. Methods: Published and in-house generated 10x Genomics single cell RNAseq data in tumor and normal samples from gastric cancer patients were aggregated, including 64 tumor samples and 27 pre-cancerous samples and 12 adjacent normal samples. The R package Seurat (version 4.0) was applied for data QC and downstream analysis. High quality cells were clustered using highly variable genes and cell types were annotated by curated marker genes. To identify malignant epithelial cells, a gastric cancer signature was derived using matched tumor and normal samples from TCGA gastric cancer patients. Gastric tumor samples were also leveraged to develop a HER2 signature and TCGA breast tumor samples were used to validate the signature. HER2+ malignant cells were identified by re-clustering malignant epithelial cells using the HER2 signature. Results: 345,361 high-quality single cells were profiled, representing major cell types within tumor microenvironment. Among 59,861 epithelial cells, 22,770 malignant cells were identified with high expression of a gastric cancer signature. Copy number alterations (aneuploid) were highly enriched in inferred malignant cells compared with non-malignant cells (48.6% vs 1.4%, p&lt;2.2×10 -16 , Fisher’s exact test). Further clustering analysis identified 10 subclusters with divergent expression of cancer oncogenic pathways, highlighting the vast heterogeneity of tumor origin. A Her2 amplification signature was derived using TCGA gastric cancer cohort (AUC=0.99) and validated in breast cancer cohort (AUC=0.93). Applying this signature to malignant cells, HER2+ cells were identified in a majority of tumors, with various proportions. In an independent data set, the percentage of HER2+ malignant cells is highly concordant with clinical HER2+ status, indicating the potential use of single cell data to supplement HER2+ clinical testing for treatment selection. Conclusions: This meta-analysis of single cell RNAseq data provides a comprehensive snapshot of tumor heterogeneity in gastric cancers, with aberrance in multiple oncogenic pathways observed in patients. The HER2+ cell classifier developed here holds the potential to complement standard clinical testing and enable personalized medicine, warranting further validation.
<i>TP53</i> gain of function mutation as a prognostic factor in high-methylated metastatic colorectal cancer: Translational research of TRICOLORE study.
Authors: Kota Ouchi, Shonosuke Wakayama, Shin Takahashi, Yasuhide Yamada, Yoshito Komatsu, Ken Shimada, Tatsuro Yamaguchi, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka
Journal: Journal of Clinical Oncology (2023)

179 Background: TP53 tumor suppressor gene is frequently inactivated by loss-of-function mutations. Some of the mutations gain additional oncogenic functions and are known as gain-of-function (GOF) mutations. This study analyzed the association among primary tumor site (PS), genome-wide DNA methylation status (GWMS), and TP53 mutation subtypes about prognosis in metastatic colorectal cancer (mCRC). Methods: Tumor tissues of mCRC patients registered in the TRICOLORE Study (clinical trial number) were analyzed for GWMS and TP53 mutation as translational research and were classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC) for GWMS, and wild-type , GOF mutation and non-GOF mutation for TP53 mutation. Overall survival (OS) was compared between single or combined subgroups, and Cox regression analysis was performed to identify factors contributing to OS. Results: A total of 209 patients were analyzed, HMCC and LMCC were 60 (28.7%) and 149 (71.3%), respectively. TP53 wild-type , GOF mutation and non-GOF mutation were 35 (16.7%), 79 (37.8%) and 95 (45.5%), respectively. HMCC showed a significantly worse prognosis than LMCC (median OS 25.3 vs. 40.3 months, P &lt; 0.01, hazard ratio 1.87). Combining GWMS and TP53 mutation subtypes about prognosis, the HMCC/GOF (n = 26) group had a significantly poorer prognosis than the other three groups including HMCC/non-GOF (n = 22), LMCC/GOF (n = 53), and LMCC/non-GOF groups (n = 73) (median OS 17.7, 35.3, 40.3, 41.2 months, p = 0.007, p &lt; 0.001, p &lt; 0.001, respectively). The HMCC/GOF group had a poorer prognosis than the other 3 groups regardless of the PS. In the multivariate analysis in the GOF mutation subgroup, HMCC (p &lt; 0.01) was the only poor prognostic factor, while right-sided colon cancer (p = 0.03) and RAS mutations (p = 0.01) were significant poor prognostic factors in the multivariate analysis in the non-GOF mutation subgroup. Conclusions: TP53 gain of function mutations are independent poor prognostic factors in high-methylated metastatic colorectal cancer.
Rectal cancer–specific subtyping using transcriptomics datasets derived from treatment-naive patients to assess novel prognostic signatures and key differences to CMS-based subtyping.
Authors: Jochen Prehn, Batuhan Kisakol, Anna Matveeva
Journal: Journal of Clinical Oncology (2023)

235 Background: Molecular subtyping in colorectal cancer provided novel insights into tumour heterogeneity and delivered new prognostic signatures. Existing methods (such as CMS-based subtyping) were generated without much consideration of differences in expression profiles between colon and rectal cancer tissues. Moreover, stage 2 and 3 rectal cancer patients often receive neo-adjuvant radio-chemotherapy which may impact on gene expression when determined from resection samples. Methods: We investigated possible differences between treatment-naive colon and rectal cancers at the molecular level. We collected mRNA expression profiles for rectal and colon cancer samples available from Gene Expression Omnibus (GEO) database (n=2139) and applied batch-effect correction using ComBat. Results: To explore whether CMS subtypes changed after neoadjuvant chemoradiation in rectal cancers, we analysed rectal tumour samples from 40 patients where both pre-operative biopsies and resections after chemoradiotherapy were available. More than half of samples shifted from CMS1-3 to CMS4 after patients received chemoradiotherapy. We therefore focused our further analysis on treatment-naive rectal cancers. We observed that CMS-based subtyping showed different prognostic potential in treatment-naïve colon vs. rectal cancers. Rectal cancers had significantly better disease-free survival (DFS) when assigned to CMS 2 or 4 compared to colon cancers. This suggested differences in disease biology that were not captured by CMS subtyping. We next aimed to identify molecular subtypes in rectal cancers, and identified three prevalent rectal-specific subtypes (RSS) by applying hierarchical clustering in 182 untreated rectal cancer samples. We used gene co-expression network analysis to define functional gene modules to identify these subtypes. Based on the gene modules’ signatures, we built a classifier to predict our new subtypes in different transcriptomics datasets (n=692). We observed that RSS1 had better disease-free survival (DFS), whereas RSS2 exhibited worse short-term DFS (less than 3 years) and RSS3 showed worse long-term DFS (3+ years). We discovered the deactivation of EGFR, MAPK and WNT pathways on RSS3 as well as high CD8+ infiltration and low CD4+ counts in these tumours. RSS2 exhibits low plasma cell and regulatory T-cell abundance and high activations of TGF-β, NF-κB, and TNF-α. We also observed high EMT, angiogenesis and inflammatory response in this subtype. Lastly, RSS1 showed high expression on MYC target and low activity on angiogenesis genes. Moreover, the immune and inflammatory responses were also lower than in the other subtypes. Conclusions: Rectal-specific subtypes are of prognostic importance and provide new insight into molecular disease pathways and potential targets.
The association between trophoblast cell surface antigen 2 expression and nivolumab monotherapy in patients with advanced gastric cancer.
Authors: Toru Kadono, Hirokazu Shoji, Hidekazu Hirano, Natsuko Okita Okita, Satoru Iwasa, Atsuo Takashima, Ken Kato
Journal: Journal of Clinical Oncology (2023)

438 Background: Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein which is associated with cancer growth. Overexpression of TROP2 in advanced gastric cancer (AGC) is known as a poor prognostic factor. However, the association between TROP2 expression and prognosis in patient with AGC treated with nivolumab (NIVO) is not known. Methods: Patients who received NIVO monotherapy as third- or later-line treatment (NIVO group) and those who received only fluoropyrimidine, platinum and taxanes (non-NIVO group) at our hospital between 2015 and 2019 were enrolled. High TROP2 expression was defined as ≥50% positive tumor cells with weak to moderate membranous staining or ≥10% tumor cells with strong membranous staining using immunohistochemistry. Overall survival from first-line chemotherapy (OS) and progression-free survival (PFS) from starting of NIVO were compared according to TROP2 expression and combined positivity score (CPS). Results: Of 111 patients, 61 were in the NIVO group and 50 were in the non-NIVO group. Patient characteristics in the NIVO/non-NIVO groups were median age 67 (range, 41-83)/64.5 (29-80) years; performance status 0, 20 (33%)/23 (46%); lymph node metastasis 41 (67%)/23 (46%); peritoneal metastasis 32 (53%)/26 (52%); liver metastasis 11 (18%)/6 (12%); lung metastasis 4 (7%)/4 (8%); TROP2 high 55 (90%)/43 (86%). Patient characteristics at starting of NIVO did not differ between TROP2 high and low in the NIVO group. Of 55 patients with TROP2 high, 22 patients (40%) were CPS≥1. In the non-NIVO group, OS from first-line chemotherapy did not differ between TROP2 high and low (median, 16.2 months [95%CI, 13.6-19.2] vs. 26.2 months [95%CI, 7.7-NA], HR 0.97, p=0.946). Meanwhile, in the NIVO group, patients with TROP2 high had significantly longer OS from first line chemotherapy than those with TROP2 low (median survival, 23.5 months [95%CI, 17.2-31.2] vs. 19.2 months [95%CI, 10.7-NA], HR 0.40, p=0.04). Progression-free survival (PFS) from starting of NIVO tended to be longer in TROP2 high group than those in TROP2 low group (median, 1.9 months [95%CI, 1.6-2.3] vs. 0.6 months [95%CI, 0.2-NA], HR 0.62, p=0.26). OS from first-line chemotherapy and PFS from starting of NIVO in patients with TROP2 high did not differ between CPS≥1 and CPS&lt;1 (OS median, 24.0 months [95%CI, 13.8-39.7] vs. 23.2 months [95%CI, 17.0-32.4], HR 0.87, p=0.69; PFS median, 1.9 months [95%CI, 1.6-3.5] vs. 2.0 months [95%CI, 1.4-2.8], HR 0.90, p=0.72). Conclusions: Higher TROP2 expression related to longer survival in the patients with AGC treated with NIVO monotherapy.
Endoscopic prediction of depth of tumor invasion in early gastric cancer in the upper third of the stomach.
Authors: Hee Seok Moon, Cnuhgi Cnuhgi
Journal: Journal of Clinical Oncology (2023)

406 Background: The endoscopic features of early gastric cancer (EGC) arising from the upper third of the stomach (upper body, fundus, and cardia) has not been well studied. If EGC in the upper third of the stomach can be predicted to have invaded the mucosal (M) or submucosal (SM) layer, endoscopic or surgical treatment can be determined. This study evaluated the endoscopic features of EGC in the upper third of the stomach as well as risk factors for SM invasion. Methods: We retrospectively reviewed patients' medical records from a single tertiary hospital (Daejeon) and investigated endoscopic findings and clinical data. Patients with EGC in the upper third of the stomach who underwent surgery or endoscopic resection between January 2016 and April 2022 were included. Logistic regression was used to determine the risk factors of the SM cancer group. Results: In total, 173 patients were enrolled in this study: 94 with SM cancer and 79 with M cancer. Risk factors for SM invasion determined by univariate logistic regression were clubbing of converging folds (OR 6.279, p=0.000), fusion of converging folds (OR 9.179, P=0.000), irregular nodule in the central lesion (OR 2.336, p=0.016), margin with elevation (OR 2.520, P=0.031), and ulceration (OR 9.686, p=0.000). However, in the multivariate logistic regression analysis, only ulceration was identified as a risk factor (OR 6.598, p=0.007). Conclusions: In EGC occurring in the upper third of the stomach, ulceration is a risk factor for SM invasion. Surgical treatment should be considered if this characteristic is present.